scholarly journals Toward Development of a Vocal Fold Contact Pressure Probe: Sensor Characterization and Validation Using Synthetic Vocal Fold Models

2019 ◽  
Vol 9 (15) ◽  
pp. 3002 ◽  
Author(s):  
Mohsen Motie-Shirazi ◽  
Matías Zañartu ◽  
Sean D. Peterson ◽  
Daryush D. Mehta ◽  
James B. Kobler ◽  
...  
Keyword(s):  
Contact Pressure ◽  
Vocal Fold ◽  
Ground Truth ◽  
Pressure Probe ◽  
Primary Role ◽  
Novel Approach ◽  
Sensor Position ◽  
Probe Sensor ◽  
Contact Pressures

Excessive vocal fold collision pressures during phonation are considered to play a primary role in the formation of benign vocal fold lesions, such as nodules. The ability to accurately and reliably acquire intraglottal pressure has the potential to provide unique insights into the pathophysiology of phonotrauma. Difficulties arise, however, in directly measuring vocal fold contact pressures due to physical intrusion from the sensor that may disrupt the contact mechanics, as well as difficulty in determining probe/sensor position relative to the contact location. These issues are quantified and addressed through the implementation of a novel approach for identifying the timing and location of vocal fold contact, and measuring intraglottal and vocal fold contact pressures via a pressure probe embedded in the wall of a hemi-laryngeal flow facility. The accuracy and sensitivity of the pressure measurements are validated against ground truth values. Application to in vivo approaches are assessed by acquiring intraglottal and VF contact pressures using a synthetic, self-oscillating vocal fold model in a hemi-laryngeal configuration, where the sensitivity of the measured intraglottal and vocal fold contact pressure relative to the sensor position is explored.

scholarly journals Direct Measurement and Modeling of Intraglottal, Subglottal, and Vocal Fold Collision Pressures during Phonation in an Individual with a Hemilaryngectomy

2021 ◽  
Vol 11 (16) ◽  
pp. 7256
Author(s):  
Daryush D. Mehta ◽  
James B. Kobler ◽  
Steven M. Zeitels ◽  
Matías Zañartu ◽  
Emiro J. Ibarra ◽  
...  
Keyword(s):  
Vocal Fold ◽  
High Speed ◽  
Pressure Sensors ◽  
Pressure Probe ◽  
Surgical Removal ◽  
In Vivo Measurement ◽  
Dual Sensor ◽  
The Right ◽  
Collision Pressure

The purpose of this paper is to report on the first in vivo application of a recently developed transoral, dual-sensor pressure probe that directly measures intraglottal, subglottal, and vocal fold collision pressures during phonation. Synchronous measurement of intraglottal and subglottal pressures was accomplished using two miniature pressure sensors mounted on the end of the probe and inserted transorally in a 78-year-old male who had previously undergone surgical removal of his right vocal fold for treatment of laryngeal cancer. The endoscopist used one hand to position the custom probe against the surgically medialized scar band that replaced the right vocal fold and used the other hand to position a transoral endoscope to record laryngeal high-speed videoendoscopy of the vibrating left vocal fold contacting the pressure probe. Visualization of the larynx during sustained phonation allowed the endoscopist to place the dual-sensor pressure probe such that the proximal sensor was positioned intraglottally and the distal sensor subglottally. The proximal pressure sensor was verified to be in the strike zone of vocal fold collision during phonation when the intraglottal pressure signal exhibited three characteristics: an impulsive peak at the start of the closed phase, a rounded peak during the open phase, and a minimum value around zero immediately preceding the impulsive peak of the subsequent phonatory cycle. Numerical voice production modeling was applied to validate model-based predictions of vocal fold collision pressure using kinematic vocal fold measures. The results successfully demonstrated feasibility of in vivo measurement of vocal fold collision pressure in an individual with a hemilaryngectomy, motivating ongoing data collection that is designed to aid in the development of vocal dose measures that incorporate vocal fold impact collision and stresses.

scholarly journals Automatically Identifying Fusion Events between GLUT4 Storage Vesicles and the Plasma Membrane in TIRF Microscopy Image Sequences

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Jian Wu ◽  
Yingke Xu ◽  
Zhouyan Feng ◽  
Xiaoxiang Zheng
Keyword(s):  
Plasma Membrane ◽  
Ground Truth ◽  
Spot Size ◽  
Biological Research ◽  
Fusion Event ◽  
Novel Approach ◽  
Storage Vesicles ◽  
Microscopy Image ◽  
Membrane Bound

Quantitative analysis of the dynamic behavior about membrane-bound secretory vesicles has proven to be important in biological research. This paper proposes a novel approach to automatically identify the elusive fusion events between VAMP2-pHluorin labeled GLUT4 storage vesicles (GSVs) and the plasma membrane. The differentiation is implemented to detect the initiation of fusion events by modified forward subtraction of consecutive frames in the TIRFM image sequence. Spatially connected pixels in difference images brighter than a specified adaptive threshold are grouped into a distinct fusion spot. The vesicles are located at the intensity-weighted centroid of their fusion spots. To reveal the truein vivonature of a fusion event, 2D Gaussian fitting for the fusion spot is used to derive the intensity-weighted centroid and the spot size during the fusion process. The fusion event and its termination can be determined according to the change of spot size. The method is evaluated on real experiment data with ground truth annotated by expert cell biologists. The evaluation results show that it can achieve relatively high accuracy comparing favorably to the manual analysis, yet at a small fraction of time.

Maximum Interlabial Pressures in Normal Speakers

1997 ◽  
Vol 40 (2) ◽  
pp. 400-404 ◽  
Author(s):  
Virginia A. Hinton ◽  
Winston M. C. Arokiasamy
Keyword(s):  
Speech Production ◽  
Contact Pressure ◽  
Direct Evidence ◽  
Unit Area ◽  
Jaw Movement ◽  
Contractile Forces ◽  
Contact Pressures ◽  
Muscle Contractile

It has been hypothesized that typical speech movements do not involve large muscular forces and that normal speakers use less than 20% of the maximum orofacial muscle contractile forces that are available (e.g., Amerman, 1993; Barlow & Abbs, 1984; Barlow & Netsell, 1986; DePaul & Brooks, 1993). However, no direct evidence for this hypothesis has been provided. This study investigated the percentage of maximum interlabial contact pressures (force per unit area) typically used during speech production. The primary conclusion of this study is that normal speakers typically use less than 20% of the available interlabial contact pressure, whether or not the jaw contributes to bilabial closure. Production of the phone [p] at conversational rate and intensity generated an average of 10.56% of maximum available interlabial pressure (MILP) when jaw movement was not restricted and 14.62% when jaw movement was eliminated.

scholarly journals Marker for the pre-clinical development of bone substitute materials

2017 ◽  
Vol 3 (2) ◽  
pp. 711-715
Author(s):  
Michael de Wild ◽  
Simon Zimmermann ◽  
Marcel Obrecht ◽  
Michel Dard
Keyword(s):  
Bone Graft ◽  
Mechanical Stability ◽  
Clinical Performance ◽  
Ex Vivo ◽  
Region Of Interest ◽  
Defect Site ◽  
Novel Approach ◽  
Bone Substitute Materials ◽  
Clinical Experiments

AbstractThin mechanically stable Ti-cages have been developed for the in-vivo application as X-ray and histology markers for the optimized evaluation of pre-clinical performance of bone graft materials. A metallic frame defines the region of interest during histological investigations and supports the identification of the defect site. This standardization of the procedure enhances the quality of pre-clinical experiments. Different models of thin metallic frameworks were designed and produced out of titanium by additive manufacturing (Selective Laser Melting). The productibility, the mechanical stability, the handling and suitability of several frame geometries were tested during surgery in artificial and in ex-vivo bone before a series of cages was preclinically investigated in the female Göttingen minipigs model. With our novel approach, a flexible process was established that can be adapted to the requirements of any specific animal model and bone graft testing.

scholarly journals Unraveling the molecular pathobiology of vocal fold systemic dehydration using an in vivo rabbit model

PLoS ONE ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. e0236348
Author(s):  
Naila Cannes do Nascimento ◽  
Andrea P. dos Santos ◽  
M. Preeti Sivasankar ◽  
Abigail Cox
Keyword(s):  
Vocal Fold ◽  
Rabbit Model

scholarly journals Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryosuke Nakamura ◽  
Nao Hiwatashi ◽  
Renjie Bing ◽  
Carina P. Doyle ◽  
Ryan C. Branski
Keyword(s):  
Vocal Fold ◽  
Vocal Folds ◽  
Nuclear Accumulation ◽  
Smad Pathway ◽  
Surgical Interventions ◽  
Smad Signaling ◽  
Iatrogenic Damage ◽  
Tgf Β1

AbstractVocal fold (VF) fibrosis is a major cause of intractable voice-related disability and reduced quality of life. Excision of fibrotic regions is suboptimal and associated with scar recurrence and/or further iatrogenic damage. Non-surgical interventions are limited, putatively related to limited insight regarding biochemical events underlying fibrosis, and downstream, the lack of therapeutic targets. YAP/TAZ integrates diverse cell signaling events and interacts with signaling pathways related to fibrosis, including the TGF-β/SMAD pathway. We investigated the expression of YAP/TAZ following vocal fold injury in vivo as well as the effects of TGF-β1 on YAP/TAZ activity in human vocal fold fibroblasts, fibroblast-myofibroblast transition, and TGF-β/SMAD signaling. Iatrogenic injury increased nuclear localization of YAP and TAZ in fibrotic rat vocal folds. In vitro, TGF-β1 activated YAP and TAZ in human VF fibroblasts, and inhibition of YAP/TAZ reversed TGF-β1-stimulated fibroplastic gene upregulation. Additionally, TGF-β1 induced localization of YAP and TAZ in close proximity to SMAD2/3, and nuclear accumulation of SMAD2/3 was inhibited by a YAP/TAZ inhibitor. Collectively, YAP and TAZ were synergistically activated with the TGF-β/SMAD pathway, and likely essential for the fibroplastic phenotypic shift in VF fibroblasts. Based on these data, YAP/TAZ may evolve as an attractive therapeutic target for VF fibrosis.

scholarly journals Artificial Tumor Microenvironments in Neuroblastoma

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1629
Author(s):  
Colin H. Quinn ◽  
Andee M. Beierle ◽  
Elizabeth A. Beierle
Keyword(s):  
Extracellular Matrix ◽  
Three Dimensional ◽  
Therapeutic Interventions ◽  
3D Bioprinting ◽  
Culture Studies ◽  
In Vivo Models ◽  
Novel Treatments ◽  
Tumor Microenvironments ◽  
Novel Approach

In the quest to advance neuroblastoma therapeutics, there is a need to have a deeper understanding of the tumor microenvironment (TME). From extracellular matrix proteins to tumor associated macrophages, the TME is a robust and diverse network functioning in symbiosis with the solid tumor. Herein, we review the major components of the TME including the extracellular matrix, cytokines, immune cells, and vasculature that support a more aggressive neuroblastoma phenotype and encumber current therapeutic interventions. Contemporary treatments for neuroblastoma are the result of traditional two-dimensional culture studies and in vivo models that have been translated to clinical trials. These pre-clinical studies are costly, time consuming, and neglect the study of cofounding factors such as the contributions of the TME. Three-dimensional (3D) bioprinting has become a novel approach to studying adult cancers and is just now incorporating portions of the TME and advancing to study pediatric solid. We review the methods of 3D bioprinting, how researchers have included TME pieces into the prints, and highlight present studies using neuroblastoma. Ultimately, incorporating the elements of the TME that affect neuroblastoma responses to therapy will improve the development of innovative and novel treatments. The use of 3D bioprinting to achieve this aim will prove useful in developing optimal therapies for children with neuroblastoma.

scholarly journals Simulating a Ground Truth for Transit Time Analysis of Indicator Dilution Curves

2020 ◽  
Vol 6 (3) ◽  
pp. 268-271
Author(s):  
Michael Reiß ◽  
Ady Naber ◽  
Werner Nahm
Keyword(s):  
Transit Time ◽  
Sampling Rate ◽  
Ground Truth ◽  
Indicator Dilution ◽  
Cross Sectional ◽  
In Vivo Measurements ◽  
Multiple Indicator Dilution ◽  
Transit Times ◽  
Dilution Curves

AbstractTransit times of a bolus through an organ can provide valuable information for researchers, technicians and clinicians. Therefore, an indicator is injected and the temporal propagation is monitored at two distinct locations. The transit time extracted from two indicator dilution curves can be used to calculate for example blood flow and thus provide the surgeon with important diagnostic information. However, the performance of methods to determine the transit time Δt cannot be assessed quantitatively due to the lack of a sufficient and trustworthy ground truth derived from in vivo measurements. Therefore, we propose a method to obtain an in silico generated dataset of differently subsampled indicator dilution curves with a ground truth of the transit time. This method allows variations on shape, sampling rate and noise while being accurate and easily configurable. COMSOL Multiphysics is used to simulate a laminar flow through a pipe containing blood analogue. The indicator is modelled as a rectangular function of concentration in a segment of the pipe. Afterwards, a flow is applied and the rectangular function will be diluted. Shape varying dilution curves are obtained by discrete-time measurement of the average dye concentration over different cross-sectional areas of the pipe. One dataset is obtained by duplicating one curve followed by subsampling, delaying and applying noise. Multiple indicator dilution curves were simulated, which are qualitatively matching in vivo measurements. The curves temporal resolution, delay and noise level can be chosen according to the requirements of the field of research. Various datasets, each containing two corresponding dilution curves with an existing ground truth transit time, are now available. With additional knowledge or assumptions regarding the detection-specific transfer function, realistic signal characteristics can be simulated. The accuracy of methods for the assessment of Δt can now be quantitatively compared and their sensitivity to noise evaluated.

scholarly journals HSP90-dependent PUS7 overexpression facilitates the metastasis of colorectal cancer cells by regulating LASP1 abundance

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Dan Song ◽  
Ming Guo ◽  
Shuai Xu ◽  
Xiaotian Song ◽  
Bin Bai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Intellectual Development ◽  
Molecular Mechanisms ◽  
Hsp90 Inhibitor ◽  
Pseudouridine Synthase ◽  
Novel Approach ◽  
Cell Metastasis ◽  
Underlying Mechanisms

Abstract Background Pseudouridine synthase (PUS) 7 is a member of the PUS family that catalyses pseudouridine formation. It has been shown to be involved in intellectual development and haematological malignancies. Nevertheless, the role and the underlying molecular mechanisms of PUS7 in solid tumours, such as colorectal cancer (CRC), remain unexplored. This study elucidated, for the first time, the role of PUS7 in CRC cell metastasis and the underlying mechanisms. Methods We conducted immunohistochemistry, qPCR, and western blotting to quantify the expression of PUS7 in CRC tissues as well as cell lines. Besides, diverse in vivo and in vitro functional tests were employed to establish the function of PUS7 in CRC. RNA-seq and proteome profiling analysis were also applied to identify the targets of PUS7. PUS7-interacting proteins were further uncovered using immunoprecipitation and mass spectrometry. Results Overexpression of PUS7 was observed in CRC tissues and was linked to advanced clinical stages and shorter overall survival. PUS7 silencing effectively repressed CRC cell metastasis, while its upregulation promoted metastasis, independently of the PUS7 catalytic activity. LASP1 was identified as a downstream effector of PUS7. Forced LASP1 expression abolished the metastasis suppression triggered by PUS7 silencing. Furthermore, HSP90 was identified as a client protein of PUS7, associated with the increased PUS7 abundance in CRC. NMS-E973, a specific HSP90 inhibitor, also showed higher anti-metastatic activity when combined with PUS7 repression. Importantly, in line with these results, in human CRC tissues, the expression of PUS7 was positively linked to the expression of HSP90 and LASP1, and patients co-expressing HSP90/PUS7/LASP1 showed a worse prognosis. Conclusions The HSP90-dependent PUS7 upregulation promotes CRC cell metastasis via the regulation of LASP1. Thus, targeting the HSP90/PUS7/LASP1 axis may be a novel approach for the treatment of CRC.

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